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Deciphering Intratumoral Molecular Heterogeneity in Clear Cell Renal Cell Carcinoma with a Radiogenomics Platform
Durga Udayakumar1,2,3, Ze Zhang4,5, Yin Xi1,5
1Department of Radiology, UT Southwestern Medical Center, Dallas, Texas.
Summary
Dynamic contrast-enhanced MRI (DCE-MRI) noninvasively maps clear cell renal cell carcinoma (ccRCC) intratumoral heterogeneity. Imaging features predict molecular subtypes and guide therapy selection, improving treatment decisions for ccRCC patients.
Area of Science:
- Oncology
- Radiology
- Genomics
Background:
- Intratumoral heterogeneity (ITH) complicates clear cell renal cell carcinoma (ccRCC) molecular profiling and treatment selection.
- Current ITH assessments rely on limited 2D ex vivo tissue analysis.
- Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers noninvasive, whole-tumor spatial landscape evaluation.
Purpose of the Study:
- To assess DCE-MRI's potential for evaluating ccRCC ITH.
- To develop a radiogenomics approach correlating imaging features with molecular subtypes.
- To investigate spatial imaging features for predicting molecular subtypes using histopathology and transcriptome data.
Main Methods:
- Prospective study of 49 ccRCC patients undergoing pre-nephrectomy DCE-MRI.
- Surgical specimens sectioned to align with MRI acquisition planes.
- RNA sequencing of 80 multi-region tumor samples correlated with DCE-MRI percent enhancement in spatially colocalized regions.
- Clinical applicability assessed in 19 metastatic RCC patients treated with antiangiogenic drugs or checkpoint inhibitors.
Main Results:
- DCE-MRI revealed tumor features linked to angiogenesis and inflammation, varying within and across ccRCC tumors.
- Angiogenesis and inflammation were found to coexist and spatially anti-correlate within the same tumor.
- MRI contrast enhancement identified phenotypes in metastatic RCC patients showing better response to antiangiogenic therapy.
Conclusions:
- DCE-MRI can noninvasively characterize ccRCC ITH, providing insights into angiogenesis and inflammation.
- Findings suggest imaging-based approaches offer a more comprehensive understanding than biopsy samples alone.
- Radiogenomics correlation highlights DCE-MRI's potential for guiding therapy selection in ccRCC.
